Clinical evaluation of suspected deep vein thrombosis guides the decision to anticoagulate prophylactically but does not impact the decision to perform after hours duplex venous scanning or increase its yield.

OBJECTIVE: The utility of after-hours duplex venous scanning (DVS) for suspected deep vein thrombosis (DVT) in emergency department (ED) patients has been debated. Availability of safe prophylactic low molecular weight heparin, cost containment efforts, and retention of scarce sonographers have to be balanced against 24/7 demand for services. We determined the incidence of DVT in DVS ordered after-hours, correlation between Wells' score and prophylactic anticoagulation as well as urgently performed DVS, and complications of delaying DVS until regular hours. METHODS: Records of all ED encounters between July 1, 2009 and June 30, 2010 associated with a DVS ordered after-hours were reviewed. The decisions to prophylactically anticoagulate and whether to perform DVS urgently or delayed until regular hours were at the discretion of the ED physician and a vascular surgeon. DVS findings, number of urgent and delayed studies, Wells' scores, D-dimers, and outcomes were recorded. RESULTS: DVT was found in 12% (22) of 181 DVS ordered after-hours. DVT was found in 19% of 42 DVS done urgently and in 10% of 139 DVS delayed an average 10 hours 17 minutes (P = NS). All patients had Wells' scores and 43 had D-dimers. Furthermore, 76% of patients with a Wells' score ≥3 had prophylactic anticoagulation whereas only 39% of patients with a Wells' score <3 had prophylactic anticoagulation (P = .0001). In contrast, 36% of patients with a Wells' score ≥3 had urgent DVS and 20% of patients with a Wells' score <3 had urgent DVS (P = NS). Prophylactic anticoagulation was given to 86% of patients eventually found to have DVT vs 40% of patients eventually found to have no DVT (P < .0001). There were no pulmonary emboli or bleeding complications. CONCLUSIONS: The incidence of DVT in ED patients who had urgent after-hours DVS was no different than in those whose DVS was delayed until regular hours. High pretest probability can be achieved with clinical evaluation prior to DVS, and this guided the decision to prophylactically anticoagulate but did not impact the decision to perform urgent DVS. Most patients eventually found to have DVT did receive prophylactic anticoagulation, and delay of DVS did not result in complications. We believe that most patients in whom there is high clinical suspicion for DVT can safely get prophylactic anticoagulation and delayed DVS. Patients in whom there is low clinical suspicion should not get urgent DVS.

Toxicity and outcomes associated with high-dose rate brachytherapy for medically inoperable endometrial cancer.

PURPOSE: To evaluate toxicity in inoperable endometrial cancer (EC) treated with definitive radiation therapy (RT). MATERIALS AND METHODS: Patients treated with definitive RT for EC were retrospectively reviewed. EQD2 values were calculated for bladder, rectum, and sigmoid. Acute and late toxicities were retrospectively graded. Descriptive statistical analysis was performed. RESULTS: Fifty-one patients were included. The majority of patients had endometrioid histology (N = 46, 90.2%) and Grade 1 disease (N = 32, 62.75%). Thirty-seven patients (72.5%) were treated with image-guided BT (IGBT) and 14 (27.5%) with two-dimensional BT. Forty patients (78.4%) received EBRT + BT and 11 (21.57%) received BT alone. No grade 2 (G2) or higher toxicities were reported with BT alone. G2 or higher acute toxicities with EBRT + BT were G2 proctitis (N = 2, 5.0%) and G3 proctitis (N = 1, 2.5%). Late toxicities included G3 vaginal stenosis (N = 1, 2.5%), proctitis (N = 1, 2.5%), enteritis (N = 1, 2.5%), and one G4 gastrointestinal bleed. One- and 2-year local control were 100% with BT alone and 93% and 89%, respectively, with EBRT + BT. One- and 2-year locoregional control were 100% with BT and 97% and 93%, respectively, with EBRT + BT. Recurrence-free survival was 89% at 1 and 2 years with BT alone compared to 87% and 80% with EBRT + BT. One- and 2-year overall survival were 88% and 72% with BT alone compared to 94% and 84% with EBRT + BT. There were no statistically significant differences in cancer control between the two groups. CONCLUSIONS: Women with inoperable EC treated with definitive RT have low toxicity rates and durable local control.

A microRNA-based signature predicts local-regional failure and overall survival after pancreatic cancer resection.

Resectable pancreatic adenocarcinoma (PC) is generally managed with surgery followed by chemotherapy, but the role of postoperative chemoradiation (pCRT) is controversial. We sought to identify a microRNA (miRNA) expression profile associated with higher risk for local-regional recurrence (LRR), which might help identify patients that may benefit from pCRT. Total RNA was isolated from viable tumor from 88 patients who underwent PC resection with or without chemotherapy, but did not receive radiation. Digital miRNA expression profiling was performed and risk scores were calculated based on the expression levels of the four most significantly correlated miRNAs, and dichotomized about the median to detect correlations between risk group, LRR and overall survival (OS). Two cohorts from The Cancer Genome Atlas (TCGA) and Seoul National University (SNU) were used for validation. Patients with high-risk scores had significantly worse LRR (p = 0.001) and worse OS (p = 0.034). Two-year OS rates for the high- and low-risk groups were 27.7% and 52.2%, respectively. On multivariable analysis, the risk score remained significantly associated with LRR (p = 0.018). When validated on TCGA data, a high-risk score was associated with worse OS on univariate (p = 0.03) and multivariable analysis (p = 0.017). When validated on the SNU cohort, a high-risk score was likewise associated with worse OS (p = 0.042). We have developed a 4-miRNA molecular signature that is associated with risk of LRR and OS after PC resection and validated on two separate cohorts. This signature has the potential to select patients most likely to benefit from pCRT, and should be tested further.

Intraoperative electron beam radiotherapy for locoregionally persistent or recurrent head and neck cancer.

BACKGROUND: To report our institutional experience with intraoperative radiotherapy for persistent or recurrent head and neck cancer. METHODS: Sixty-one patients were treated with salvage surgery and intraoperative radiation therapy (IORT). Fifty-eight patients (95%) had previously received external beam radiotherapy (EBRT) as a component of their definitive therapy. Forty-four patients (72%) had squamous cell carcinoma (SCC). Surgical margins were positive in 28 patients (46%). IORT was prescribed to a median dose of 12.5 Gy (range, 10-17.5). Twenty-three patients (38%) received a course of postoperative EBRT (median 45 Gy). Clinical outcomes were retrospectively reviewed and univariate analysis was performed using log-rank tests to correlate clinical outcomes with histology, surgical margin, and adjuvant therapy. RESULTS: Median follow-up among surviving patients was 15.9 months. Median progression-free survival (PFS) and overall survival (OS) were 9.8 and 19.1 months, respectively. One- and 2-year rates of locoregional control (LRC) were 59% and 35%, respectively. One- and 2-year rates of PFS were 39% and 19%, respectively. One- and 2-year rates of OS were 62% and 42%, respectively. Overall survival was better for non-SCC histology (P = .03). For SCC patients, negative surgical margin showed a trend toward improved PFS (P = .09) and OS (P = .06). There was one grade-5 toxicity due to carotid rupture. CONCLUSIONS: IORT has shown effective LRC and OS with an acceptably low rate of severe toxicity at our institution. OS was significantly better for non-SCC histology. For SCC patients, there is a trend toward improved PFS and OS associated with negative surgical margins.

Molecular profiling of locally-advanced rectal adenocarcinoma using microRNA expression (Review).

Treatment for locally-advanced rectal cancer (LARC) typically consists of neoadjuvant chemoradiation followed by total mesorectal excision. Recently, there has been growing interest in non-operative management for patients who are medically-inoperable or wish to avoid surgical morbidity and permanent colostomy. Approximately 50% of patients who receive pre-operative neoadjuvant chemoradiation develop some degree of pathologic response. Approximately 10-20% of patients are found to have a complete pathologic response, a finding which has frequently been shown to predict better clinical outcomes, including local-regional control, distant metastasis and survival. Many recent studies have evaluated the role of molecular biomarkers in predicting response to neoadjuvant therapy. MicroRNAs (miRNAs) are an emerging class of biomarkers that have the potential to predict which patients are most likely to benefit from pre-operative therapy and from a selective surgical approach. Here, we review the published literature on microRNAs as prognostic and predictive biomarkers in rectal cancer after pre-operative therapy. In the future, the development of prospectively validated miRNA signatures will allow clinical implementation of miRNAs as prognostic and predictive signatures in LARC.

Prognostic Value of Primary Tumor Volume Changes on kV-CBCT during Definitive Chemoradiotherapy for Stage III Non-Small Cell Lung Cancer.

INTRODUCTION: Kilovoltge cone beam computed tomography (kV-CBCT) allows for tumor localization and response assessment during definitive chemoradiotherapy for locally advanced NSCLC. We hypothesize that significant tumor volume loss occurs early during radiotherapy and that the extent of volume loss correlates with clinical outcomes. METHODS: A total of 52 patients with locally advanced NSCLC treated with definitive chemoradiotherapy were reviewed. kV-CBCT images were used to contour primary gross tumor volumes at four time points during treatment. Patients were dichotomized according to absolute and relative volume changes at each time point. Statistical analyses were performed to evaluate correlations between volume changes and clinical outcomes. RESULTS: The median gross tumor volumes were 77.1, 48.3, 42.5, and 29.9 cm3 for fractions 1, 11, 21, and final, respectively. Greater relative volume loss between fractions 1 and 21 correlated with improved distant control (hazard ratio [HR] = 0.35, 95% confidence interval [CI]: 0.13-0.94, p = 0.038) and overall survival (HR = 0.40, 95% CI: 0.16-0.98, p = 0.046). Greater relative volume loss between fractions 11 and 21 correlated with improved progression-free survival (HR = 0.39, 95% CI: 0.17-0.88, p = 0.02) and trended toward improved overall survival (HR = 0.43, 95% CI: 0.17-1.06, p = 0.07). On multivariate analysis, greater relative volume loss between fractions 11 and 21 correlated with improved progression-free survival (HR = 0.39, 95% CI: 0.16-0.97, p = 0.041) and overall survival (HR = 0.31, 95% CI: 0.11-0.88, p = 0.027). CONCLUSIONS: Significant primary tumor volume loss occurs early during radiotherapy for locally advanced NSCLC. Greater relative tumor volume loss during treatment correlates with improved disease control and overall survival. Thus, kV-CBCT has potential to be used as a practical prognostic imaging marker.

Prognostic value of microRNA expression levels in pancreatic adenocarcinoma: a review of the literature.

BACKGROUND: Clinical and pathologic markers of prognosis and patterns of failure help guide clinicians in selecting patients for adjuvant therapy after surgical resection for pancreatic adenocarcinoma (PDAC). Recent studies have reported the prognostic utility of microRNA profiling in numerous malignancies. Here, we review and summarize the current literature regarding associations between microRNA expression and overall survival in PDAC patients. MATERIALS AND METHODS: We conducted a systematic search in the PubMed database to identify all primary research studies reporting prognostic associations between tumor and/or serum microRNA expression and overall survival in PDAC patients. Eligible articles were reviewed by the authors and relevant findings are summarized below. RESULTS: We found 53 publications that fit our search criteria. In total, 23 up-regulated and 49 down-regulated miRNAs have been associated with worse overall survival. MiR-21 is the most commonly reported miRNA, appearing in 19 publications, all of which report aberrant over-expression and association with shorter survival in PDAC. Other miRNAs that appear in multiple publications include miR-10b, -21, -34a, -155, -196a, -198, -200c, -203, -210, -218, -222, and -328. We summarize the preclinical and clinical data implicating these miRNAs in various molecular signaling pathways and cellular functions. CONCLUSIONS: There is growing evidence that miRNA expression profiles have the potential to provide tumor-specific prognostic information to assist clinicians in more appropriately selecting patients for adjuvant therapy. These molecules are often aberrantly expressed and exhibit oncogenic and/or tumor suppressor functions in PDAC. Additional efforts to develop prognostic and predictive molecular signatures, and further elucidate miRNA mechanisms of action, are warranted.